Cerebral Blood Flow In Children Research Articles

Abnormal cerebral blood flow in children with developmental stuttering.

Stuttering affects approximately 5% of children; however, its neurological basis remains unclear. Identifying imaging biomarkers could aid in early detection. Accordingly, we investigated resting-state cerebral blood flow (CBF) in children with developmental stuttering. Pulsed arterial spin labelling magnetic resonance imaging was utilised to quantify CBF in 35 children with developmental stuttering and 27 healthy controls. We compared normalised CBF between the two groups and evaluated the correlation between abnormal CBF and clinical indicators. Compared with healthy controls, the stuttering group exhibited decreased normalised CBF in the cerebellum lobule VI bilaterally, right cuneus, and left superior occipital gyrus and increased CBF in the right medial superior frontal gyrus, left rectus, and left dorsolateral superior frontal gyrus. Additionally, normalised CBF in the left cerebellum lobule VI and left superior occipital gyrus was positively correlated with stuttering severity. Children who stutter display decreased normalised CBF primarily in the cerebellum and occipital gyrus, with increased normalised CBF in the frontal gyrus. Additionally, the abnormal CBF in the left cerebellum lobule VI and leftsuperior occipital gyrus was associated with more severe symptoms, suggesting that decreased CBF in these areas may serve as a novel neuroimaging clue for stuttering. Stuttering occurs in 5% of children and often extends into adulthood, which may negatively affect quality of life. Early detection and treatment are essential. We used pulsed arterial spin labelling magnetic resonance imaging to visualise the resting-state cerebral blood flow (CBF) in children who stutter and healthy children. Normalised CBF was decreased in stutterers in the cerebellum and occipital gyrus and increased in the frontal gyrus. Stuttering severity was linked to abnormal normalised CBF in the left cerebellum lobule VI and left superior occipital gyrus, suggesting that CBF may serve as a novel neuroimaging clue for stuttering.

Abstract TMP10: Children With Sickle Cell Anemia Have Impaired Cerebrovascular Reactivity

Introduction: Sickle Cell Anemia (SCA) causes lower hemoglobin, leading to increased cerebral blood flow (CBF) to maintain cerebral oxygen metabolism (CMRO 2 ). Although CBF rises in childhood to meet higher CMRO 2 demands, further compensatory increases in CBF in children with SCA may tap into a limited hemodynamic reserve, increasing risk for infarct. Cerebrovascular reactivity (CVR) reflects hemodynamic reserve by measuring the vasculature’s response to vasoactive stimuli, particularly in the gray matter (GM). We hypothesized that children with SCA have lower GM CVR, regardless of CMRO 2 . Methods: We used magnetic resonance imaging of children with and without SCA to collect pseudocontinuous arterial spin labeling (pCASL) for CBF, asymmetric spin echo for oxygen extraction fraction (OEF) and blood oxygen level dependent (BOLD) data correlated with hypercapnic challenges for CVR. Lab draws confirmed Hemoglobin (Hb) values. CMRO 2 was calculated as CBF x OEF x Arterial Oxygen Content (1.36 x Hb x SpO 2 ). Continuous variable differences between groups were analyzed using the Mann-Whitney U test, and categorical variables using the Fisher’s exact test. Linear regression assessed the relationship between CVR and Hb. Reported significant relationships survived multiple comparisons correction. Results: A total of 35 participants, ages 8–22 years had quality CVR data [9 SCA subjects (5 male) and 26 controls (9 male)]. Of these, 8 SCA and 20 controls had adequate quality metabolic data. The groups are matched by age (p=0.56) and sex (p=0.43). Children with SCA had higher GM CBF (62.0 v 49.3 mL/100g/min; p=0.03), but similar GM CMRO 2 (1.81 v 1.42 mL/100g/min; p=0.07) than controls. GM CVR was significantly lower in SCA than controls (0.17 v 0.27 %/mmHg; p=0.0003). Lower CVR was associated with lower Hb (Figure) after adjusting for age and sex (p <0.0001). Conclusion: Lower GM CVR in children with SCA indicates a lower hemodynamic reserve, likely related to the degree of anemia.

Cerebral blood flow in children with persisting postconcussive symptoms and posttraumatic headache at 2 weeks postconcussion.

Persisting postconcussive symptoms (pPCS), particularly headache, can significantly disrupt children's recovery and functioning. However, the underlying pathophysiology of these symptoms remains unclear. The goal in this study was to determine whether pPCS are related to cerebral blood flow (CBF) at 2 weeks postconcussion. The authors also investigated whether variations in CBF can explain the increased risk of acute posttraumatic headache (PTH) in female children following concussion. As part of a prospective, longitudinal study, the authors recruited children 5-18 years old who were admitted to the emergency department of a tertiary pediatric hospital with a concussion sustained within 48 hours of admission. Participants underwent pseudocontinuous arterial spin labeling MRI at 2 weeks postconcussion to quantify global mean gray and white matter perfusion (in ml/100 g/min). Conventional frequentist analysis and Bayesian analysis were performed. Comparison of recovered (n = 26) and symptomatic (n = 12) groups (mean age 13.15 years, SD 2.69 years; 28 male) found no differences in mean global gray and white matter perfusion at 2 weeks postconcussion (Bayes factors > 3). Although female sex was identified as a risk factor for PTH with migraine features (p = 0.003), there was no difference in CBF between female children with and without PTH. Global CBF was not associated with pPCS and female PTH at 2 weeks after pediatric concussion. These findings provide evidence against the use of CBF measured by arterial spin labeling as an acute biomarker for pediatric concussion recovery.

The longitudinal evolution of cerebral blood flow in children with tuberous sclerosis assessed by arterial spin labeling magnetic resonance imaging may be related to cognitive performance.

To study longitudinal changes in tuber and whole-brain perfusion in children with tuberous sclerosis complex (TSC) using arterial spin labeling (ASL) perfusion MRI and correlate them with pathological EEG slow wave activity and neurodevelopmental outcomes. Retrospective longitudinal cohort study of 13 children with TSC, 3 to 6 serial ASL-MRI scans between 2 months and 7 years of age (53 scans in total), and an EEG examination performed within 2 months of the last MRI. Tuber cerebral blood flow (CBF) values were calculated in tuber segmentation masks, and tuber:cortical CBF ratios were used to study tuber perfusion. Logistic regression analysis was performed to identify which initial tuber characteristics (CBF value, volume, location) in the first MRI predicted tubers subsequently associated with EEG slow waves. Whole-brain and lobar CBF values were extracted for all patient scans and age-matched controls. CBF ratios were compared in patients and controls to study longitudinal changes in whole-brain CBF. Perfusion was reduced in tubers associated with EEG slow waves compared with other tubers. Low tuber CBF values around 6 months of age and large tuber volumes were predictive of tubers subsequently associated with EEG slow waves. Patients with severe developmental delay had more severe whole-brain hypoperfusion than those with no/mild delay, which became apparent after 2 years of age and were not associated with a higher tuber load. Dynamic changes in tuber and brain perfusion occur over time. Perfusion is significantly reduced in tubers associated with EEG slow waves. Whole-brain perfusion is significantly reduced in patients with severe delay. • Tubers associated with EEG slow wave activity were significantly more hypoperfused than other tubers, especially after 1 year of age. • Larger and more hypoperfused tubers at 6 months of age were more likely to subsequently be associated with pathological EEG slow wave activity. • Patients with severe developmental delay had more extensive and severe global hypoperfusion than those without developmental delay.

Assessment of cerebral blood flow in children with myopia in combination with undifferentiated connective tissue dysplasia

Background. In practice, patients with numerous undifferentiated forms of connective tissue dysplasia are more common. With regard to the combination of myopia and undifferentiated connective tissue dysplasia, one of the links in the mechanism of origin of this refractive anomaly is decreased thickness of the sclera and a change in its elastic parameters. Myopia in children often occurs against the background of impaired blood supply to the visual analyzer associated with circulatory pathology in the vertebral vessels. The purpose was to evaluate cerebral blood flow in patients with myopia in combination with undifferentiated connective tissue dysplasia. Materials and methods. The study involved 86 children (170 eyes) diagnosed with progressive myopia. All patients were consulted by related specialists to detect undifferentiated connective tissue dysplasia and underwent a complete ophthalmological exa-mination. The diagnostic coefficient of expression of phenotypic and clinical signs of undifferentiated connective tissue dysplasia was also determined using the expert table of T. Kadurina. Results. Phenotypic and clinical signs of undifferentiated connective tissue dysplasia were noted in 41 (100 %) cases when evaluating according to the criteria of T. Mil-kovskaya-Dimitrova and T. Kadurina, and in 34 (83.0 %) children du-ring screening for joint hypermobility on Beighton score. As for increased axial length of the eye in the examined patients with myopia and undifferentiated connective tissue dysplasia, it was noted that an increase had a direct correlation with the severity of undifferentiated connective tissue dysplasia, with the greatest correlation obtained in children with pronounced phenotypic manifestations in the musculoskeletal system (correlation coefficient was 0.83). Chemical regulation of carotid artery tone (respiratory failure test) is altered in the vast majority of patients with myopia. Conclusions. All children with progressive myopia are re-commended to be examined by related specialists to identify undif-ferentiated connective tissue dysplasia and hemodynamic disorders. Only a comprehensive approach to this refractive anomaly can be effective in combating its progression.

Assessment of Functional Shunting in Patients with Sickle Cell Disease

IntroductionSilent cerebral infarcts (SCI) are common in patients with sickle cell disease (SCD) and thought to be caused by a mismatch between oxygen delivery and consumption. The mechanism underlying insufficient oxygen utilization is related to severity of anemia, and paradoxically, to the elevated cerebral blood flow (CBF) observed in SCD patients. CBF is elevated as a compensatory mechanism to maintain oxygen delivery, but high CBF levels can result in rapid transit of blood through the brain capillaries, limiting offloading of oxygen to the tissue; a process called arteriovenous shunting. One way to assess functional arteriovenous shunting is to use noncontrast perfusion MRI techniques in which we can assess the signal intensity of an endogenous blood tracer when it reaches the sagittal sinus. This venous signal (VS) reflects the amount of labeled blood that has not exchanged with the brain parenchyma. Under normal physiological conditions, the VS intensity will increase approximately proportionally with CBF as we expect only some of the water to exchange with tissue as it flows by. However, it is unknown whether functional shunting scales with CBF only, or whether other hemodynamic processes play a role in patients with SCD. We hypothesize that, under pathophysiological conditions such as in SCD patients, more labeled blood may pass unexchanged through the capillaries, which results in higher VS. In the present study, we investigated functional shunting by quantifying VS and assessed its association with hemodynamic, demographic and laboratory parameters in both pediatric and adult SCD patients, and controls. In addition, VS-CBF relationship was studied by further increasing CBF after a vasodilatory challenge.MethodsWe included 28 children (mean age 12.7 ± 2.3, 9 F) and 38 adults (mean age 32.1 ± 11.2, 14 F) with SCD (HbSS and HbS), and 10 healthy race-matched adult controls (mean age 36.4 ± 15.9, 4 F). For the CBF and VS measurements, pseudo-continuous arterial spin labelling (pCASL) data were acquired using 3T MRI. We segmented the ASL blood pool in the sagittal sinus to determine a common region of interest for each group. We used these images as masks to calculate average VS. Notably, for the comparison between children and adults the ratio between VS to gray matter CBF was used (VGR) instead of the VS, to take into account higher CBF in children. To get more insight into the oxygen utilization, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2) were calculated. In adult participants acetazolamide (ACZ) was used as a vasodilatory challenge. The hematologic laboratory parameters hemoglobin (Hb) and LDH were used as markers of anemia and hemolysis, respectively.ResultsVS as a marker of cerebral shunting was higher in both adult and pediatric patients with SCD as compared to controls (p<0.01) and increased after ACZ administration in all groups (p<0.01) (Fig. 1A). VS was significantly associated with CBF both before (R 2=0.59, p<0.001) and after ACZ administration (R 2=0.57, p<0.001) in all groups (Fig. 1B). To test the impact of demographics and hematological parameters on the presence of shunting, VS was corrected for CBF (VS CBF) and the residuals were used in multiple linear regression analysis against age, sex, blood flow velocity in the brain feeding arteries, participant groups, hydroxyurea, Hb and LDH. Cerebral shunting, reflected by VS CBF showed significant association with Hb (Fig. 1C). In addition, we added OEF, CMRO 2 and ACZ condition as additional parameters in adults and used a linear mixed model to accommodate the repeated measures dependencies. A negative association between the level of cerebral shunting (VS CBF) and CMRO 2 was found (β=-0.79, p<0.001) in all groups (Fig. 1C), and in adult patients with SCD, CMRO 2, Hb (β=-14.2 p<0.001) and LDH (β=0.13, p=0.002) were significant predictors of VS CBF.ConclusionOur results show that the VS in the sagittal sinus on ASL images can be used to assess functional arteriovenous shunting in the brain. Given its negative association with CMRO 2 in combination with the negative association with hemoglobin and positive correlation with LDH, this functional shunting seems to reflect pathophysiologic shunting related to higher disease severity. Future studies will focus on the relation between functional shunting and the prevalence of SCI, investigating its link to aberrant capillary oxygen exchange in SCD. [Display omitted] DisclosuresVaclavu: Philips Healthcare: Research Funding. Biemond: GBT: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria; Sanquin: Research Funding.

Normalization of Cerebral Hemodynamics after Hematopoietic Stem Cell Transplant in Children with Sickle Cell Anemia

▪BackgroundChildren with Sickle Cell Anemia (SCA) are at high risk for overt or silent strokes, and this risk may be mitigated by hematopoietic stem cell transplant (HSCT). Our research group has shown that when cerebral oxygen delivery is compromised due to anemia in SCA, the cerebral blood flow (CBF) and brain oxygen extraction fraction (OEF) increase to maintain brain tissue oxygen delivery. We used novel magnetic resonance imaging (MRI) sequences to measure OEF and CBF in children with SCA treated with HSCT, testing the hypothesis that after HSCT, OEF and CBF will be similar to control values.MethodsChildren with SCA were enrolled in a pilot prospective, observational study of MRI-measured OEF and CBF. Brain MRI exams were performed without sedation on a 3T Siemens scanner. The MRI protocol included fluid-attenuated inverse recovery (FLAIR) sequences in two planes to evaluate for strokes, asymmetric spin echo to measure tissue-level OEF, and pseudo-continuous arterial spin labeling perfusion-weighted imaging to measure CBF. HSCT recipients underwent paired brain MRI 1-2 months before and >1 year after HSCT. Controls, non-anemic siblings of SCA patients, had a single brain MRI. Pre- and post-HSCT CBF and OEF were compared within subjects and between the HSCT and control cohorts using non-parametric tests. Bivariate correlations between OEF or CBF and hemoglobin (Hb) or Hb S concentrations were tested with Spearman's rho. The level of significance was specified as p < 0.05 after adjustment by the Benjamini-Hochberg procedure.ResultsFour children (two male, median age 10 years, range 8-21 years) underwent HSCT: one had prior overt stroke, one had silent strokes, and two had no neuroimaging abnormalities. All received a reduced intensity preparative regimen of alemtuzumab, melphalan, and fludarabine. One subject received marrow from an HLA-matched unrelated donor without Hb S trait; two received marrow from HLA-identical siblings. One child who had rejected a HSCT from an HLA-identical sibling underwent re-conditioning with antithymocyte globulin and cyclophosphamide and received CD-34-selected peripheral stem cells from the same donor. All sibling donors had Hb S trait. Brain MRIs of 20 non-anemic sibling controls of median age 11 years (range 6-17 years) were included for comparison.Median OEF and CBF were significantly elevated pre-HSCT compared to controls (OEF median 0.355 vs 0.288, p = 0.012; CBF median 99.8 vs 65.1 ml/100 g/min, p = 0.018; Figure). Median post-HSCT OEF and CBF were lower than pre-HSCT values (OEF median 0.270 vs 0.355, CBF median 65.1 vs 99.8 ml/100 g/min, p = 0.13 for both), but these analyses had low power to detect significant differences due to the small sample size. Post-HSCT, recipients' OEF and CBF were similar to controls (OEF median 0.270 vs 0.288, p=0.18; CBF median CBF 65.1 vs 75.8 ml/100 g/min, p = 0.42). None of the HSCT recipients had new overt or silent strokes on FLAIR imaging or developed severe acute or chronic GVHD after HSCT.Pre-HSCT, recipients were anemic compared to controls (median Hb 9.8 vs 12.8 g/dl, p = 0.018). Pre-HSCT Hb S concentrations were lower than expected for SCA due to recent red blood cell transfusions (median 50.6%, range 39.7-77.6%). At the post-HSCT imaging timepoint, recipients' anemia had resolved (median Hb 12.4 g/dl, range 11.3-15.7 g/dl), and Hb S concentrations were consistent with their donors' levels. When all pre- and post-HSCT measurements were compared, OEF had a strong negative correlation with Hb (Spearman's rho = -0.905, p = 0.002) and a strong positive correlation with Hb S concentration (Spearman's rho = 0.970, p < 0.001). CBF had a weaker negative correlation with Hb (Spearman's rho = -0.714, p = 0.047) and positive correlation with Hb S concentration (Spearman's rho = 0.731, p = 0.040).ConclusionIn this cohort, children with SCA had normalization of OEF and CBF after successful HSCT. OEF elevation was strongly correlated with Hb S concentration and inversely correlated with Hb concentration in these HSCT recipients. Our data suggest that when curative HSCT corrects hemolytic anemia, OEF and CBF normalize. This physiologic change may provide protection against strokes following HSCT for SCA. [Display omitted] DisclosuresHulbert:Pfizer: Other: Spouse employment at Pfizer. Fields:Proclara Biosciences: Equity Ownership.

Effect of combination of acupuncture and psychological intervention on attention, response inhibition and cerebral blood flow in children with attention deficit hyperactivity disorder

To observe the clinical curative effect on attention deficit hyperactivity disorder (ADHD) and explore the relevant mechanism of acupuncture in treatment. A total of 100 ADHD children were randomized into an observation group (50 cases, 2 cases dropped off) and a control group (50 cases, 1 case dropped off). In the control group, the routine psychological intervention was used. In the observation group, on the base of the treatment as the control group, acupuncture was applied to Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Sanyinjiao (SP 6), Baihui (GV 20), Sishencong (EX-HN 1), etc., once daily, for 3 months. The Cambridge neuropsychological tests automated battery (CANTAB) was adopted to evaluate attention and response inhibition in two groups before and after treatment. Digi-Lite color transcranial Doppler was used to measure cerebral arterial blood velocity. The therapeutic effect was compared between the two groups. Regarding evaluation of attention, the mean delay time in the observation group after treatment was shorter than that before treatment and that in the control group separately (P<0.05), and rapid visual information processing A' statistics (RVP A') value was higher than that before treatment and that in the control group separately (P<0.05). For evaluation of response inhibition, the number of Go signal error, the time of stop signal response and the number of stop Go signal error after treatment were all reduced as compared with those before treatment in the two groups (P<0.05). The number of stop signal error was also reduced after treatment as compared with that before treatment in the observation group (P<0.05). The number of Go signal error and the number of stop signal error in the observation were lower than those in the control group (P<0.05). After treatment, the average flow velocity of bilateral posterior cerebral artery (PCA) was increased than that before treatment in the two groups (P<0.05). The average flow velocity of the left middle cerebral artery (MCA-L) and bilateral anterior cerebral artery (ACA) after treatment was increased than that before treatment in the observation group (P<0.05), and the average flow velocity of left PCA, MCA-L and bilateral ACA in the observation group was faster than that in the control group (P<0.05). The total effective rate was 90.5% (19/21) in the observation group, remarkably higher than 50.0% (11/22) in the control group in children with attention deficit (P<0.05). The total effective rate was 83.3% (40/48) in the observation group, also higher than 63.3% (31/49) in the control group (P<0.05). Acupuncture combined with psychological intervention may improve attention and response inhibition in ADHD children, which is possibly related to the regulation of cerebral blood flow.

Assessment of Cerebral Blood Flow and Oxygen Extraction in Pediatric Sickle Cell Disease with Non-Invasive Diffuse Optical Spectroscopies

Introduction: Cerebral infarcts and associated cognitive impairments are a devastating consequence of sickle cell disease (SCD). While the underlying mechanisms are poorly understood, infarctions are thought to arise from anemia-induced microvascular perfusion abnormalities and subsequent reduced cerebrovascular reserve that is insufficient to meet tissue metabolic demands. Thus, quantification of abnormalities in microvascular cerebral blood flow (CBF) and oxygen extraction (OEF) may be useful in identifying infarct risk and monitoring therapeutic efficacy. Unfortunately, current modalities that quantify microvascular hemodynamics (e.g., PET, MRI) are prohibitively expensive, have limited availability, and require anesthesia in children &amp;lt;6y, making them inappropriate as routine monitoring tools. Transcranial Doppler ultrasound (TCD) is currently the standard screening tool for overt stroke risk in pediatric SCD, but it only measures blood flow velocity in the large arteries, which is a poor surrogate for microvascular perfusion in sickle cell disease. Diffuse optical spectroscopies (specifically near-infrared frequency-domain spectroscopy, FDNIRS, and diffuse correlation spectroscopy, DCS) offer a low-cost, non-invasive alternative for bedside monitoring of tissue-level OEF and CBF. We previously demonstrated that FDNIRS/DCS are sensitive to elevations in resting-state OEF and CBF in children with sickle cell disease compared to healthy controls (Lee, Neurophotonics 2019), consistent with previous studies using MRI and PET. In this feasibility study, we demonstrate these optical techniques are sensitive to altered cerebral hemodynamics in sickle patients who are 1) undergoing chronic transfusion, and 2) experiencing vaso-occlusive pain episodes (VOE). Methods: To date, we have recruited 6 pediatric patients with sickle cell disease undergoing chronic transfusion (5 females and 1 male, 6 - 14 y, mean ± std hemoglobin change pre- to post-transfusion = 1 ± 0.8 g/dL) and 4 patients admitted to the Emergency department for VOE (2 females and 2 males, 8 - 18 y, mean±std hemoglobin on admission = 8.9 ± 1.6 g/dL). For the transfusion cohort, FDNIRS/DCS measurements were made immediately prior to the start of transfusion and again immediately upon completion. For the VOE cohort, FDNIRS/DCS measurements were made upon hospital admission. For all FDNIRS/DCS assessments, a custom sensor was manually held over right and left forehead to assess oxygen extraction fraction (OEF, %) and an index of microvascular cerebral blood flow (CBFi, cm2/s) (Lee, Neurophotonics 2019). Hemispheric results were averaged to yield a mean of each measured parameter. Total measurement time was less than 15 minutes. Results: In the cohort undergoing chronic transfusion, one patient data was excluded due to poor DCS signal quality. Of the remaining 5 patients, OEF and CBFi decreased after transfusion by a median of -6.4% and -30.0%, respectively (Fig 1A, B). The FDNIRS-measured OEF decrease is comparable to previous results with MRI (Guilliams, Blood 2017) that quantified both cortical OEF and CBF response to transfusion in a similarly aged cohort. However, the DCS-measured CBFi decrease is more prominent than previously reported (30% vs. 9%). The enhanced sensitivity of DCS to CBF in sickle cell disease was reported in our recent study and is likely attributed to the confounding influences of hematocrit on the DCS-measured CBFi (Sathialingam, Biomed Opt Exp 2020). In the cohort measured during VOE, one patient data was excluded due to poor FDNIRS data quality. Of the remaining 3 subjects, OEF was elevated compared to healthy controls and was on the upper range of values measured in a cohort of otherwise subjects with sickle cell disease who were without clinical complications and were measured as part of a separate study (Fig. 1C). Conclusion: These data demonstrate how FDNIRS/DCS may be used as a simple, low-cost tool for bedside assessment of cerebral hemodynamics in non-sedated sickle children that could be used to track brain health over time, particularly during periods thought to be prone to hemodynamic instability like transfusion or VOEs. Although ~20% of data was discarded in this dataset due to improper sensor positioning leading to poor signal quality, we have recently implemented real-time quality control feedback to ensure our data passes quality criteria. Disclosures Lam: Sanguina, Inc: Current equity holder in private company.

Study of cerebral hemodynamics in children with small anomalies of the heart development

Annotation. Diseases of the cardiovascular system occupy a leading place in the structure of non-infectious pathology. In the literature, small abnormalities of the development of the heart are described as abnormally located trabeculae or additional chords in the left ventricle of the heart or mitral valve prolapse. At present, the problem of cerebral hemodynamic disorders in children with them is insufficiently studied in medical sources. The aim of our study was to analyze cerebral hemodynamics using ultrasound dopplerography of cerebral vessels in children with abnormally attached chords (AAC) and mitral valve prolapse (MVP). We examined 64 children with AAC and 106 patients with MVP (among whom there were 90 with MVP I degree and 16 with MVP II degree) aged from 13 to 17 years, who formed the main group. The results were compared with the data of the control group, which included 23 almost healthy children also aged 13–17 years. All children underwent ultrasound dopplerography of extra- and intracranial vessels and veins of the brain. Evaluated the average values in the form of M±m. The values of the differences between the indicators of the two samples were evaluated by Student’s parametric criterion (t) using a special program such as Microsoft Excel. In children with MVP I deg. we found a pronounced violation of blood flow in a. vertebralis on both sides with diagnostically significant (р&lt;0,05) decrease in the mean values of systolic and diastolic blood flow indexes. The elasticity of the vessels was high relative to the control group. In children with grade II MVP, a decrease of the blood flow was observed within a. vertebralis basin, which was accompanied by a significant (р&lt;0,05) decrease of systolic and diastolic velocities on both sides in comparison with control group. An increase (р&lt;0,05) in systolic-diastolic index (Sd) and circulatory resistance index (Ri) was noted in both sides, indicating a simultaneous increase in the tone and elasticity of these vessels. In patients with AAC there was a decrease in systolic and diastolic velocities in the a.vertebralis on both sides with increase of Sd relative to the control group. Thus, cerebral blood flow in children with AAC and MVP is generally satisfactory. There are changes in the elastic and tonic properties of blood vessels in these children. The results of the study will be useful to narrow specialists for timely and adequate rehabilitation of patients with MARS.

Effects of food supplementation on cognitive function, cerebral blood flow, and nutritional status in young children at risk of undernutrition: randomized controlled trial

ObjectiveTo assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition.DesignRandomized controlled trial.Setting10 villages in Guinea-Bissau.Participants1059 children...

Disrupted Regional Cerebral Blood Flow in Children With Newly-Diagnosed Type 1 Diabetes Mellitus: An Arterial Spin Labeling Perfusion Magnetic Resonance Imaging Study.

Object: Diabetes is associated with cerebral vascular dysfunction and increased vascular cognitive impairment. The objective of this study was to use arterial spin labeling (ASL) perfusion-weighted magnetic resonance imaging to investigate whether cerebral perfusion was changed in newly-diagnosed children with type 1 diabetes mellitus (T1DM) and the possible relationship between aberrant cerebral blood flow (CBF) with cognitive as well as clinical variables.Methods: Between January 2017 and February 2018, 34 children with newly-diagnosed T1DM and 34 age, gender, and education-matched healthy controls were included. Three dimensional pseudo-continuous ASL perfusion MRI was used to evaluate CBF. A conventional T2WI sequence was added to exclude intracranial disease. Regions with CBF differences between T1DM children and the controls were detected via voxel-wise comparisons in REST software. Associations among the result of neuropsychological test, clinical variables, and CBF values of different brains were investigated by using partial correlation analysis.Results: Compared with the controls, T1DM children show decreased CBF in the left calcarine and postcentral gyrus, and right precentral gyrus. The perfusion in the postcentral gyrus was positively correlated with IQ performance. No significant correlations were found between CBF and HbA1c, blood glucose level before imaging and IQ in other brain regions in T1DM children.Conclusion: There is an abnormal cerebral perfusion in children with newly diagnosed T1DM. The visual and sensorimotor areas are brain areas where perfusion is prone to change at the beginning of T1DM. Our study provided clues for cerebral pathophysiological changes in the initial stage of T1DM.

Cerebral blood flow in children with syndromic craniosynostosis: cohort arterial spin labeling studies.

In comparison with the general population, children with syndromic craniosynostosis (sCS) have abnormal cerebral venous anatomy and are more likely to develop intracranial hypertension. To date, little is known about the postnatal development change in cerebral blood flow (CBF) in sCS. The aim of this study was to determine CBF in patients with sCS, and compare findings with control subjects. A prospective cohort study of patients with sCS using MRI and arterial spin labeling (ASL) determined regional CBF patterns in comparison with a convenience sample of control subjects with identical MRI/ASL assessments in whom the imaging showed no cerebral/neurological pathology. Patients with SCS and control subjects were stratified into four age categories and compared using CBF measurements from four brain lobes, the cerebellum, supratentorial cortex, and white matter. In a subgroup of patients with sCS the authors also compared longitudinal pre- to postoperative CBF changes. Seventy-six patients with sCS (35 female [46.1%] and 41 male [53.9%]), with a mean age of 4.5 years (range 0.2-19.2 years), were compared with 86 control subjects (38 female [44.2%] and 48 male [55.8%]), with a mean age of 6.4 years (range 0.1-17.8 years). Untreated sCS patients < 1 year old had lower CBF than control subjects. In older age categories, CBF normalized to values observed in controls. Graphical analyses of CBF by age showed that the normally expected peak in CBF during childhood, noted at 4 years of age in control subjects, occurred at 5-6 years of age in patients with sCS. Patients with longitudinal pre- to postoperative CBF measurements showed significant increases in CBF after surgery. Untreated patients with sCS < 1 year old have lower CBF than control subjects. Following vault expansion, and with age, CBF in these patients normalizes to that of control subjects, but the usual physiological peak in CBF in childhood occurs later than expected.

Association of cognitive function with cerebral blood flow in children with moyamoya disease.

The cognitive effects of main cerebral artery occlusive lesions are unclear in children with moyamoya disease (MMD). The authors aimed to investigate cognitive function in the presurgical phase of pediatric patients with MMD with no apparent brain lesions. In this prospective, observational, single-center study, 21 children (mean age 10 ± 3.0 years, range 5-14 years) diagnosed with MMD at Hokkaido University Hospital between 2012 and 2018 were enrolled. A cross-sectional evaluation of intellectual ability was performed using the Wechsler Intelligence Scale for Children-Fourth Edition at the initial diagnosis. rCBF was measured using [123I] N-isopropyl p-iodoamphetamine/SPECT. The associations among clinical factors, disease severity, regional cerebral blood flow (rCBF), and intelligence test scores were also examined. The mean full-scale intelligence quotient (FIQ) was 101.8 ± 12.5 (range 76-125) in children with no apparent brain lesions. A significant difference in the intelligence scale index score was observed, most frequently (42.9%) between working memory index (WMI) and verbal comprehension index (VCI; VCI - WMI > 11 points). Regional CBF was significantly reduced both in the left and right medial frontal cortices (left: 61.3 ± 5.3 ml/100 g/min, right 65.3 ± 5.3 ml/100 g/min; p < 0.001) compared to the cerebellum (77.8 ± 6.8 ml/100 g/min). There was a significant association of rCBF in the left dorsolateral prefrontal cortex (DLPFC) with FIQ (r = 0.46, p = 0.034), perceptual reasoning index (PRI; r = 0.44, p = 0.045), and processing speed index (PSI; r = 0.44, p = 0.045). There was an association between rCBF of the left medial frontal cortex and PSI (r = 0.49, p = 0.026). Age of onset, family history, ischemic symptoms, and angiographic severity were not associated with poor cognitive performance. Although average intellectual ability was not reduced in children with MMD, the association of reduced rCBF in the left DLPFC and medial frontal cortex with FIQ, PRI, and PSI suggests mild cognitive dysfunction due to cerebral hypoperfusion.

Noninvasive optical assessment of resting-state cerebral blood flow in children with sickle cell disease

Sickle cell disease (SCD) is a genetic blood disorder that has profound effects on the brain. Chronic anemia combined with both macro- and microvascular perfusion abnormalities that arise from stenosis or occlusion of blood vessels increased blood viscosity, adherence of red blood cells to the vascular endothelium, and impaired autoregulatory mechanisms in SCD patients all culminate in susceptibility to cerebral infarction. Indeed, the risk of stroke is 250 times higher in children with SCD than in the general population. Unfortunately, while transcranial Doppler ultrasound (TCD) has been widely clinically adopted to longitudinally monitor macrovascular perfusion in these patients, routine clinical screening of microvascular perfusion abnormalities is challenging with current modalities (e.g., positron emission tomography and magnetic resonance imaging) given their high-cost, requirement for sedation in children year, and need for trained personnel. We assess the feasibility of a low-cost, noninvasive optical technique known as diffuse correlation spectroscopy (DCS) to quantify an index of resting-state cortical cerebral blood flow (BFI) in 11 children with SCD along with 11 sex- and age-matched healthy controls. As expected, BFI was significantly higher in SCD subjects compared to healthy controls ( ). Within SCD subjects, BFI was inversely proportional to resting-state arterial hemoglobin levels ( ), consistent with expected anemia-induced compensatory vasodilation that aims to maintain adequate oxygen delivery to the tissue. Further, in a subset of patients measured with TCD ( ), DCS-measured blood flow was correlated with TCD-measured blood flow velocity in middle cerebral artery ( ), although the trend was not statistically significant ( ). These results are consistent with those of several previous studies using traditional neuroimaging techniques, suggesting that DCS may be a promising low-cost tool for assessment of tissue-level CBF in pediatric SCD.

Asymmetric Dimethylarginine Levels and Its Correlation to Cerebral Blood Flow in Children with Sickle Cell Anemia.

Asymmetric dimethylarginine (ADMA) level may play a role in the pathogenesis of cerebrovascular stroke in Children with Sickle Cell Anemia (SCA). To assess the plasma level of ADMA in children with SCA and its correlation to cerebral blood flow. This is a cross sectional study was carried out on 30 children with homozygous SCA under follow up in the Out Patients Clinic, Pediatric Department at Tanta University Hospital and 30 healthy children as a control group. Both groups had undergone the following investigations: Complete blood count, lactate dehydrogenase enzyme, and plasma level of ADMA by a commercial ADMA ELISA Kit. Trans-cranial Doppler were done for both groups. ADMA plasma level was significantly higher in-patient group in comparison to the control group (p < 0.001), with a mean value 1.43 ± 0.20μmol/l, 0.48 ± 0.16μmol/l respectively. The time-averaged mean maximum velocities for middle cerebral artery, anterior cerebral artery, inferior cerebral artery and posterior cerebral artery were significantly different between patient and control group, p < 0.05. Trans-cranial Doppler data revealed that, 86.7% of patients have low velocity (< 70cm/s) and 13.3% having very low velocity (< 10cm/s) while control group have normal velocity. There was a significant negative correlation between ADMA plasma levels and cerebral blood flow. Elevated ADMA levels may have a role in the pathogenesis of the decreased cerebral blood flow in children with SCA.

Cerebral blood flow in children and adolescents several years after concussion

ABSTRACTObjectives: The long-term effects of concussion in youth remain poorly understood. The objective of this study was to determine the association between history of concussion and cerebral blood flow (CBF) in youth.Methods: A total of 53 children and adolescents with a history of concussion (n = 37) or orthopaedic injury (OI; n = 16) were considered. Measures included pseudo-continuous arterial spin labelling magnetic resonance imaging to quantify CBF, post-concussion symptoms, psychological symptoms, and cognitive testing.Results: Participants (mean age: 14.4 years, 95% CI = 13.8–15.4, range = 8–19) were on average 2.7 years (95% CI = 2.2–3.1) post-injury. Youth with a history of concussion had higher parent-reported physical, cognitive, anxiety, and depression symptoms than children with OI, but the groups did not differ on self-reported symptoms (post-concussive or psychological) or cognitive testing. Global CBF did not differ between groups. Regional CBF analyses suggested that youth with a history of concussion had hypoperfusion in posterior and inferior regions and hyperperfusion in anterior/frontal/temporal regions as compared to those with OI. However, neither global nor regional CBF were significantly associated with demographics, pre-injury functioning, number of concussions, time since injury, post-concussive symptoms, psychological symptoms, or cognitive abilities.Conclusions: Youth with a history of concussion demonstrate differences in regional CBF (not global CBF), but without clear clinical expression.

Alterations in cerebral blood flow in children with congestive heart failure due to ventricular septal defect

We aimed to investigate the effect of ventricular septal defect (VSD) and heart failure on cerebral blood flow (CBF) in children, whether heart failure treatment improves CBF, and if there is any relationship between CBF and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level. Forty children with VSD (13 with heart failure) aged between 1 and 36months were studied. The control group comprised 25 healthy children in the same age group. Maximum, minimum, and mean blood flow velocities and pulsatility indices of the right and left middle cerebral arteries were assessed using transcranial Doppler ultrasonography. Measurements of CBF and serum NT-proBNP levels were repeated in patients with heart failure a month post-heart failure treatment initiation. The groups were also compared in terms of defect diameters, cardiac structural changes, left ventricular systolic function, and findings related to pulmonary hypertension determined by echocardiography. Correlations between echocardiographic measurements and CBF parameters were analyzed. Although no significant difference was found between patient and control groups for CBF, right and left maximum CBF velocities significantly increased posttreatment in patients with heart failure (P=.04 and P=.01, respectively). Serum NT-proBNP levels in children with VSD associated with heart failure were significantly higher than those in children with VSD alone (P=.04) or in healthy children (P<.001). NT-proBNP levels were negatively correlated with right and left maximum CBF velocities (r=-0.39, P=.013 and r=-0.32, P=.043, respectively). Although no significant difference was found in CBF velocity among the study groups, increase in the CBF velocity post heart failure treatment and negative correlations between CBF velocity and both the VSD diameter and NT-proBNP levels indicate that the hemodynamic status due to VSD associated with heart failure has an effect on CBF.

Regional Cerebral Blood Flow in Children and Young Adults with Chronic Kidney Disease.

Purpose To investigate the pathophysiologic effects of chronic kidney disease (CKD) on brain function in children with CKD by correlating cerebral blood flow (CBF) with clinical and behavioral indexes. Materials and Methods In this prospective study, 73 pediatric patients with CKD (mean age, 15.80 years ± 3.63; range, 9-25 years) and 57 control subjects (mean age, 15.65 years ± 3.76; range, 9-25 years) were recruited. CBF measurements were acquired with an MRI arterial spin labeling scheme. Neurocognitive measurements were performed with traditional and computerized neurocognitive batteries. Clinical data were also collected. Group-level global and regional CBF differences between patients with CKD and control subjects were assessed. Regression analyses were conducted to evaluate the associations among regional CBF, clinical variables, and cognitive performance. Results Patients with CKD showed higher global CBF compared with control subjects that was attributable to reduced hematocrit level (mean, 60.2 mL/100 g/min ± 9.0 vs 56.5 mL/100 g/min ± 8.0, respectively). White matter CBF showed correlation with blood pressure (r = 0.244, P = .039), a finding suggestive of altered cerebrovascular autoregulation. Regional CBF differences between patients and control subjects included regions in the "default mode" network. In patients with CKD, positive extrema in the precuneus showed a strong correlation with executive function (ρ = 0.608, P = .001). Conclusion Systemic effects of estimated glomerular filtration rate, hematocrit level, and blood pressure on CBF and alterations in regional CBF may reflect impaired brain function underlying neurocognitive symptoms in CKD. These findings further characterize the nature of alterations in brain physiologic features in children, adolescents, and young adults with CKD.

Effects of whole blood viscosity and plasma NOx on cardiac function and cerebral blood flow in children with chronic kidney disease

Background/aim: The aim of the study was to investigate the effects of whole blood viscosity and plasma nitric oxide on cerebral and cardiovascular risks associated with chronic kidney disease. Materials and methods: The study group consisted of 40 pediatric patients and 21 healthy control subjects. Hematologic and biochemical variables, viscosity and plasma nitric oxide levels, echocardiographic findings, and middle cerebral artery blood flow velocity were examined. Results: Viscosity values of patients were significantly lower than those of the control group. Lower values of hematocrit, total protein, and albumin and higher values of ferritin in all patient groups resulted in significantly low viscosity levels. Plasma nitric oxide levels were higher in all patient groups than those in the controls. No statistically significant difference was present in middle cerebral artery blood flow velocity between the patient and control groups. Even when systolic functions were normal, the patient group had significant deterioration in diastolic functions, suggesting morbidity and mortality risks. Conclusions: Cerebral blood flow velocities were not affected by viscosity and nitric oxide levels, suggesting that cerebral circulation has the ability to make adaptive modulation. The metabolism of nitric oxide levels needs further investigation and studies in patients with chronic renal disease.